Humans sense odorants in the environment via a large number of olfactory sensory neurons (OSNs) in the olfactory epithelium in the nose. Each OSN expresses only one olfactory receptor (OR) gene out of a large family of OR genes (˜350 in humans and ˜1200 in mice). OSNs project their axon to the olfactory bulb (OB) in the brain and all OSNs that express the same OR gene converge to one or a few areas in OB, called glomeruli. Individual odorants can excite multiple types of OR, and each OR can be excited by multiple odorants. Thus, coding of odorants is combinatorial.
The discovery of OR gene family (Buck & Axel, 1991) opened a new era in olfactory research. Multiple OR genes have been cloned and their properties have been studied systematically. In mice, studies have been carried out by tagging an identified OR gene with a florescent protein (e.g. GFP). OSNs that express a GFP tagged OR gene can be identified in the epithelium, as well as in the corresponding glomerulus in the OB, thus allowing for the study of the response property of this OR. In this way, for a given receptor it is possible to screen a large number of odorants and characterize its molecular receptive range. However, each odorant can excite multiple receptors, and it is very difficult to find all receptors responsive to a given odorant. In addition, it is even more difficult to find which of the receptors responsive to a given odorant are the most sensitive.
Currently it is possible to measure the response of a large population of OSNs in two types of assays: one directed to the epithelium and the other to the OB. In the first assay an odorant is presented to either isolated OSNs or the whole epithelium, and either Ca+2 imaging or electrophysiological recordings are used to measure response to this odorant. In the second type of assay, the response is measured in the OB usually by observing Ca+2 dynamics in the glomerulus. In both cases, it is difficult to establish genetic identity of OSNs responsive to a specific odorant, i.e., to identify genes of ORs excited by the odorant. An additional shortcoming is that OB imaging usually allows monitoring of only the dorsal area of the OB, which constitutes ˜20% of all OB glomeruli.
It would be useful to identify specific ORs for given odorants, however there is no high throughput method for doing this. In addition, it is even more difficult to identify the relative sensitivities of different ORs for a given odorant. The more sensitive receptors may play special role in odor identification.